Epoxides serve useful roles as intermediates in biochemical pathways, but being chemically reactive, they also can produce deleterious effects such as alkylation of DNA and proteins, framshift mutations, and tissue necrosis. In view of this the long range objectives of this work are 1) to determine the extent to which chemically reactive epoxide metabolites of drugs and xenobiotic materials are responsible for the damage which occurs following administration of the epoxide precursor, 2) to elucidate enzymatic mechanisms of epoxide metabolism and to develop effective in vivo inhibitors for these enzymes, and 3) to develop methods of enhancing in vivo pathways of epoxide transformation as a way to prevent their toxic effects. BIBLIOGRAPHIC REFERENCE: R.P. Hanzlik, M. Edelman, W.J. Michaely, and G. Scott, "Enzymatic Hydration of (18 O)-Epoxides. The Role of Nucleophilic Mechanisms." J. Amer. Chem. Soc., 98, 1952 (1976), in press.